A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases.

Unlabelled: Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAM) to pulmonary diseases remains poorly understood due to difficulty in accessing them from human donors and their rapid phenotypic change during culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies.

Pharmacological depletion of microglia alleviates neuronal and vascular damage in the diabetic CX3CR1-WT retina but not in CX3CR1-KO or hCX3CR1-expressing retina.

Diabetic retinopathy, a microvascular disease characterized by irreparable vascular damage, neurodegeneration and neuroinflammation, is a leading complication of diabetes mellitus. There is no cure for DR, and medical interventions marginally slow the progression of disease. Microglia-mediated inflammation in the diabetic retina is regulated CX3CR1-FKN signaling, where FKN serves as a calming signal for microglial activation in several neuroinflammatory models.

A 384-Well Microtiter Plate Model for Candida Biofilm Formation and Its Application to High-Throughput Screening.

Candidiasis, infections caused by Candida spp., represents one of the most common nosocomial infections afflicting an expanding number of compromised patients. Antifungal therapeutic options are few and show limited efficacy.

Our current clinical understanding of Candida biofilms: where are we two decades on?

Clinically we have been aware of the concept of Candida biofilms for many decades, though perhaps without the formal designation. Just over 20 years ago the subject emerged on the back of progress made from the bacterial biofilms, and academic progress pace has continued to mirror the bacterial biofilm community, albeit at a decreased volume. It is apparent that Candida species have a considerable capacity to colonize surfaces and interfaces and form tenacious biofilm structures, either alone or in mixed species communities.

Chlamydia trachomatis plasmid-encoding Pgp3 protein induces secretion of distinct inflammatory signatures from HeLa cervical epithelial cells.

Background: Genital Chlamydia trachomatis infection is the most common bacterial sexual transmitted disease that causes severe complications including pelvic inflammatory disease, ectopic pregnancy, and infertility in females. The Pgp3 protein encoded by C. trachomatis plasmid has been speculated to be an important player in chlamydial pathogenesis.

The Vibrio Polar Flagellum: Structure and Regulation.

Here we discuss the structure and regulation of the Vibrio flagellum and its role in the virulence of pathogenic species. We will cover some of the novel insights into the structure of this nanomachine that have recently been enabled by cryoelectron tomography. We will also highlight the recent genetic studies that have increased our understanding in flagellar synthesis specifically at the bacterial cell pole, temporal regulation of flagellar genes, and how the flagellum enables directional motility through Run-Reverse-Flick cycles.

Design, synthesis and biological activity of hybrid antifungals derived from fluconazole and mebendazole.

A novel series of triazole alcohol antifungals bearing a 5-benzoylbenzimidazol-2-ylthio side chain have been designed and synthesized as hybrids of fluconazole (a typical triazole antifungal) and mebendazole (an anthelmintic agent with antifungal activity). The title compounds were synthesized via the reaction of an appropriate oxirane and desired 2-mercaptobenzimidazole. Although there was possibility for formation of different N-substituted or S-substituted products, the structures of final compounds were assigned as thioether congeners by using C NMR spectroscopy.

Serine/Threonine Phosphatase Calcineurin Orchestrates the Intrinsic Resistance to Micafungin in the Human-Pathogenic Fungus Mucor circinelloides.

Procedures such as solid-organ transplants and cancer treatments can leave many patients in an immunocompromised state. This leads to their increased susceptibility to opportunistic diseases such as fungal infections. Mucormycosis infections are continually emerging and pose a serious threat to immunocompromised patients.

A Customized Monkeypox Virus Genomic Database (MPXV DB v1.0) for Rapid Sequence Analysis and Phylogenomic Discoveries in CLC Microbial Genomics.

Monkeypox has been a neglected, zoonotic tropical disease for over 50 years. Since the 2022 global outbreak, hundreds of human clinical samples have been subjected to next-generation sequencing (NGS) worldwide with raw data deposited in public repositories. However, sequence analysis for in-depth investigation of viral evolution remains hindered by the lack of a curated, whole genome Monkeypox virus (MPXV) database (DB) and efficient bioinformatics pipelines.

Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection.

Genital Chlamydia trachomatis infection remains a major health issue as it causes severe complications including pelvic inflammatory disease, ectopic pregnancy and infertility in females as a result of infection-associated chronic inflammation. Podoplanin, a transmembrane receptor, has been previously reported on inflammatory macrophages. Thus, strategies that specifically target podoplanin might be able to reduce local inflammation.

The current state of laboratory mycology in Asia/Pacific: A survey from the European Confederation of Medical Mycology (ECMM) and International Society for Human and Animal Mycology (ISHAM).

Introduction: Invasive fungal infections (IFIs) in Asia/Pacific are a particular threat to patients with malignancies, uncontrolled diabetes mellitus or undiagnosed/untreated human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS). Adequate and early access to diagnostic tools and antifungals is essential for IFI clinical management and patient survival.

Methods: Details on institution profile, self-perception on IFI, and access to microscopy, culture, serology, antigen detection, molecular testing, and therapeutic drug monitoring for IFI were collected in a survey.

Antifungal activity of miltefosine against both azole-susceptible and -resistant Aspergillus strains.

Miltefosine, an alkylphosphocholine, has been approved recently for the treatment of visceral leishmaniasis. Miltefosine has shown promise as a treatment for paracoccidioidomycosis, and has mixed activity against other fungi and yeast. There are limited data on the in-vitro activity of miltefosine against azole-resistant and -susceptible Aspergillus spp.

Models of microglia depletion and replenishment elicit protective effects to alleviate vascular and neuronal damage in the diabetic murine retina.

Microglia, the resident phagocytes of the retina, are believed to influence the development of retinopathy, but their exact contributions to vascular integrity and neuronal loss are unknown. Therefore, utilizing two models of microglia depletion, we aimed to deplete and repopulate microglia to clarify the contribution of microglia to neuronal loss and vascular damage in the diabetic retina in an STZ-induced model of hyperglycemia. Here, we report that 2 weeks exposure to diphtheria toxin (DTx) in diabetic CX3CR1:R26 transgenic mice induced a 62% increase in Iba1 microglia associated with an increase in TUJ1 axonal density and prevention of NeuNRBPMS neuronal loss.

In Vitro Combination of Terbinafine with Ketoconazole Against Aspergillus Species with Terbinafine High MIC Values Isolated From Otomycosis.

Otomycosis is a common mycotic infection of the external auditory canal, and Aspergillus species are one of the most frequent causative agents worldwide. The limited antifungal arsenal, the high toxicity and side effects of antifungal agents, and the growing resistance to the currently available antifungals underscore the need for new therapeutic strategies. The present study aimed to evaluate the combined in vitro efficacy of terbinafine and ketoconazole against Aspergillus species with terbinafine high MIC values isolated from patients with otomycosis.

In vitro antifungal susceptibility profile of Iranian Fusarium isolates: Emphasising on the potent inhibitory effect of efinaconazole compared to other drugs.

Background: Fusarium species are opportunistic human pathogens that remarkably cause fungal infections ranging from superficial to fatal invasive disseminated infections. Fusarium species are notoriously resistant to the majority of antifungal agents.

Objectives: Therefore, detailed studies regarding in vitro susceptibility are required and may lead to a better prognosis of severe infections.

Pathogenome comparison and global phylogeny of Escherichia coli ST1485 strains.

Escherichia coli ST1485 strains belong to the clinically important phylogroup F and have disseminated worldwide in humans, animals, and the environment. Here, we elucidated the pathogenome of a global collection of E. coli ST1485 isolates from diverse sources retrieved from public databases and a high-quality sequenced complete genome of colistin-resistant E.

Genomic Data Mining Reveals Abundant Uncharacterized Transporters in and .

and are causative agents of coccidioidomycosis, commonly known as Valley Fever. The increasing Valley Fever cases in the past decades, the expansion of endemic regions, and the rising azole drug-resistant strains have underscored an urgent need for a better understanding of biology and new antifungal strategies. Transporters play essential roles in pathogen survival, growth, infection, and adaptation, and are considered as potential drug targets.

Defibrinogenation Ameliorates Retinal Microgliosis and Inflammation in A CX3CR1-Independent Manner.

Diabetic human and murine retinas revealed pronounced microglial morphological activation and vascular abnormalities associated with inflammation. Pharmacological fibrinogen depletion using ancrod dampened microglial morphology alterations, resolved fibrinogen accumulation, rescued axonal integrity, and reduced inflammation in the diabetic murine retina.

Five-year surveillance study of clinical and environmental Triazole-Resistant Aspergillus fumigatus isolates in Iran.

Background: Invasive aspergillosis is one of the most common fungal infections and azole resistance in Aspergillus fumigatus (ARAf) is a growing medical concern in high-risk patients. To our knowledge, there is no comprehensive epidemiological surveillance study on the prevalence and incidence of ARAf isolates available in Iran.

Objectives: The study aimed to report a five-year survey of triazole phenotypes and genotype patterns concerning the resistance in clinical and environmental A.

Trends in the Prevalence of Amphotericin B-Resistance (AmBR) among Clinical Isolates of Aspergillus Species.

The challenges of the invasive infections caused by the resistant Aspergillus species include the limited access to antifungals for treatment and high mortality. This study aimed to provide a global perspective of the prevalence of amphotericin B resistance (AmBR), geographic distribution, and the trend of AmBR from 2010 to 2020. To analyze the prevalence of in vitro AmBR in clinical Aspergillus species, we reviewed the literature and identified a total of 72 articles.

HPV Integration Site Mapping: A Rapid Method of Viral Integration Site (VIS) Analysis and Visualization Using Automated Workflows in CLC Microbial Genomics.

Human papillomavirus (HPV) integration within the host genome may contribute to carcinogenesis through various disruptive mechanisms. With next-generation sequencing (NGS), identification of viral and host genomic breakpoints and chimeric sequences are now possible. However, a simple, streamlined bioinformatics workflow has been non-existent until recently.

In Vitro Antifungal Susceptibility Profile of Miltefosine against a Collection of Azole and Echinocandins Resistant Strains.

species are filamentous fungi that cause a variety of infections in humans. Because they are commonly resistant to many antifungal drugs currently available in clinical settings, research into alternative targets in fungal cells and therapeutic approaches is required. The antifungal activity of miltefosine and four comparators, amphotericin B, voriconazole, itraconazole, and caspofungin, were tested in vitro against a collection of susceptible and resistant clinical ( = 68) and environmental ( = 42) isolates.